Buildings today represent a large part of societies energy consumption. The increasing environmental awareness has sparked an interest in lowering building energy consumption and building automation systems has been recognized as an effective way of contributing to a more sustainable society. The purpose of this report is to identify the blocking and driving forces between actors in the construction industry when implementing and developing building automation systems. By understanding the blocking and driving forces of a technology in a system, an understanding can be developed of how the industry should act to increase the usage and development of certain technology. Building automation systems can be said to be a systemic innovation, that is, an innovation that affects more than one actor. As there is more than one actor affected by the innovation, systemic innovations are characterized by the complexity when enforcing it. A tool for understanding problems that different actors’ face is the technological innovation framework. This framework has laid the foundation for the analysis of the system strengths and system weaknesses when implementing and developing building automation. In addition, a literature study on technological innovation systems and systemic innovation has been conducted. By examining and evaluating collected data from 19 expert interviews based on the following seven functions presented in the technological innovation framework, five system weaknesses and four system strengths have been identified. The five system weaknesses are (1). The construction industry´s structure and working methods, (2). Lack of industrial cooperation, (3). The conservative attitude in the construction industry, (4). Limited access and development of human capital, and (5) Weak market incentives. Based on these system weaknesses, a discussion was conducted regarding the importance of coordination between the construction industry’s actors and its different disciplines. With the understanding of the four system strengths, (1). Established marked and proven technology, (2). Strong digitalization trends and positive knowledge development, (3). Increased environmental awareness and, (4). Strong urbanization trends, creates an understanding of what factors that drives the systems forward. / Byggnader representerar idag en stor del av den totala energiförbrukningen i samhället. I takt med en ökad miljömedvetenhet har intresset för att sänka byggnaders energiförbrukning blivit en allt viktigare fråga och fastighetsautomation har uppmärksammats som ett effektivt sätt för att bidra till ett mer hållbart samhälle. Syfte med denna rapport är att identifiera de systemsvagheter och systemstyrkor som finns mellan aktörerna i byggindustrin vid implementering och utveckling av fastighetsautomation. Genom att förstå systemsvagheterna och systemstyrkorna för en teknologi i ett system kan förståelse skapas för hur en industri skall agera för att kunna öka användandet och utvecklingen av en viss teknik. Fastighetsautomation kan sägas vara en systemisk innovation, det vill säga en innovation som påverkar fler än en part. I och med att flera aktörer påverkas av innovationen kännetecknas systemiska innovationer av dess komplexitet att genomföra. Ett verktyg för att förstå de bakomliggande utmaningarna för ett system är det teknologiska innovationsramverket. Ramverket har legat till grund för analysen kring systemstyrkor och systemsvagheter inom området för fastighetsautomation. Till detta har även en litteraturstudie genomförts kring teknologiska innovationssystem samt systemisk innovation. Genom att ha undersökt insamlade data från 19 expertintervjuer baserade på de sju funktionerna som presenterats i det teknologiska innovationsramverket, har fem systemsvagheter och fyra systemstyrkor kunnat identifieras. De fem systemsvagheterna är (B1). Byggindustrins uppbyggnad och arbetssätt, (B2). Bristande industriell samverkan, (B3). Byggindustrins konservativa attityd, (B4). Begränsad tillgång och utveckling av humankapital, och (B5) Svaga marknadsincitament. Baserat på systemsvagheterna förs en diskussion kring vikten av samordning mellan byggindustrins aktörer och discipliner. Med förståelsen för de fyra systemstyrkorna, (D1). Etablerad marknad och beprövad teknik, (D2). Stark digitaliseringstrend och positiv kunskaps tillförsel, (D3). Ökad miljömedvetenhet och (D4). Stark urbaniseringstrend, skapas en förståelse för faktorer som gynnar byggindustrins arbete med fastighetsautomation.

Bakgrund: Intensivvård är den högsta vårdnivån inom svensk sjukvård och omhändertar kritiskt sjuka patienter. Intensivvård innebär stora påfrestningar på patienten och förutom sin primärdiagnos finns det stor risk att drabbas av sekundära komplikationer relaterat till intensivvården. En av flera negativa konsekvenser på grund av passiviteten är intensivvårdsförvärvad svaghet (ICU-AW). Interventionen tidig mobilisering är en av flera åtgärder för att förebygga intensivvårdsförvärvad svaghet. Syfte: Syftet med studien var att beskriva evidensen för och effekter av tidig mobilisering av respiratorbehandlade vuxna patienter på intensivvårdsavdelning. Metod: Studien utformades som en systematisk litteraturöversikt och metaanalyser. Sökningar gjordes i databaserna PubMed och CINAHL. Sökningarna bestod av sökblocken Intensivvård, Respiratorbehandling och Tidig mobilisering. Metaanalyser utfördes i Review Manager. Resultat: Denna studie innehåller totalt sju RCT-studier med fokus på tidig mobilisering av respiratorbehandlade vuxna patienter, totalt 976 patienter. Tre parametrar analyserades; Dagar i respirator, Dagar på IVA och Dödlighet på IVA. Dagar i respirator och Dödlighet på IVA visade ingen statistisk signifikans. Endast parametern Dagar på IVA hade statistisk signifikans (P=0,01). Slutsats: Denna systematiska översiktsstudie och metaanalys resulterade i evidens för förkortad vårdtid på intensivvårdsavdelning vid tidig mobilisering av respiratorbehandlade vuxna patienter jämfört med standardmobilisering. Kortare vårdtid på intensivvårdsavdelning minskar risken för intensivvårdsförvärvad svaghet. / Background: Intensive care is the highest level of care in Swedish healthcare and takes care of critically ill patients. Intensive care involves great strain on the patients and in addition to their primary diagnosis, there is a great risk of suffering from secondary complications related to intensive care. One of several negative consequences due to inactivity is intensive care acquired weakness (ICU-AW). The early mobilization intervention is one of several interventions to prevent intensive care-acquired muscle weakness. Aim: The aim of this study was to describe the evidence for and effects of early mobilization of mechanically ventilated adult patients in the intensive care unit. Method: The study was designed as a systematic literature review and meta-analysis. Searches were performed in the PubMed and CINAHL databases. The searches consisted of the search blocks Intensive Care, Respirator Treatment and Early Mobilization. Meta-analysis were performed in the Review Manager. Results: This study contains a total of seven RCT studies focusing on early mobilization of ventilator-treated adult patients, a total of 976 patients. Three parameters were analyzed; Days in ventilator (Dagar i respirator), Days in ICU (Dagar på IVA) and Mortality in ICU (and Dödlighet på IVA). Days in ventilator and Mortality in the ICU showed no statistical significance. Only the parameter Days in ICU had statistical significance (P = 0.01). Conclusion: This systematic review study and meta-analysis resulted in evidence of shortened care time in the intensive care unit due to early mobilization of ventilator-treated adult patients compared to standard mobilization. Shorter care time in the intensive care unit reduces the risk of intensive care acquired weakness.

The present thesis, Paul's Apostolic Existence. How to understand apostle Paul when he writes about apostle Paul, investigates the issue of why Paul writes so frequently in his epistles about himself and his life. The search starts in 2 Cor 12:1-10 where Paul mentions Christ's answer to his prayer for recovery from sickness: "My grace is sufficient for you, for power is made perfect in weak- ness." This statement becomes the central point of the investigations. Their core part is exegesis of the relevant passages, mostly from Paul's letters to Corinth. The context is broadened by selected texts from the letters to the Philippians and to the Romans. In these texts, the apostle explains to the read- ers his own existence mainly by pointing out his weakness and suffering. The present thesis argues that Paul's motives for writing these texts should be looked for in his theology. He considers his recurring experience of God's power in weakness as instrumental in his mission to preach the gospel. The argument is supported by possibly precise description of the relation between Paul's apostolic existence and his preaching. This will show what benefit these texts can and should bring to their readers.

With development and impact of ICT, the method of work in many organizations has been becoming more collaborative and communicative, under which a number of organizations start to take corresponding strategies to achieve business goals and create more values. Managing Business Process is an effective and efficient way to improve productivity and performance of business activities from an organizational level. Business Process model, as a representation of Business Process, provides a big picture of Business Process, allowing organizations to acquire understanding on logical relationships among different business activities and to improve Business Process by various approaches. This study discusses the application of Business Process models on weakness identification which is related to the problem of excess inventory in supply chain with a qualitative method. It adopts three Business Process Modelling techniques to build Business Process models for a planning team involved with demand and supply planning, where four experts from the team participate in interview. The models are analyzed according to selected weakness patterns in order to identify the process weaknesses and link them with the causes of excess inventory. The result of this study gives a positive answer, which means the Business Process Models are capable to identify causes for the concrete problem of excess inventory by identifying process weaknesses.

- examination and treatment took place in ambulant facility REHAMIL s.r.o. in Lysá nad f PhDr. Jitka Malá, PhD and pneumologist MUDr. Šárka Klimešová, PhD. g's dyspnea scale, Otto inclination and reclination distance, respiratory the reduction in exertional dyspnea assessed by the Borg's dyspnea scale (p

Résumé : Introduction : L’ataxie récessive spastique de Charlevoix-Saguenay (ARSCS) est une maladie héréditaire dégénérative présentant un taux élevé de porteurs (1/22) au Saguenay-Lac-Saint-Jean, mais aussi retrouvée à l’échelle mondiale. Les personnes atteintes présentent des atteintes cérébelleuses (ataxie), neuropathiques (amyotrophie) et pyramidales (spasticité). L’ARSCS présente un portrait différent des autres types d’ataxies et il n’existe pas d’échelle de gravité spécifique pour évaluer la progression de la maladie ou évaluer l’efficacité d’un traitement. Méthodologie : Les objectifs de ce projet sont de développer et documenter les qualités métrologiques des items de la section pyramidale de l’échelle de gravité de l’ARSCS (Disease Severity Index for Autosomal Recessive Spastic Ataxia of Charlevoix-Saguenay, DSI-ARSACS). La section pyramidale a été élaborée à l’aide du modèle de développement de Streiner et Norman (2008). La planification et la construction ont été réalisées à l’aide d’une recension systématique des écrits et d’une consultation Delphi. La validité de construit (convergente et discriminatoire) et la fidélité (intraévaluateur et interévaluateurs [n=2]) ont été documentées. Vingt-huit (28) participants âgés de 18 à 59 ans ont été recrutés, selon un échantillonnage stratifié pour l’âge et le sexe. Le diagnostic devait être confirmé génétiquement. La validité convergente a été documentée avec des outils évaluant le contrôle moteur aux membres inférieurs (LEMOCOT), la gravité de la spasticité (SPRS), la mobilité (6MWT, 10mWT, échelle de Berg), le fonctionnement dans les activités quotidiennes (Index de Barthel), la participation sociale (MHAVIE) et la qualité de vie (SF-12v2). La validité discriminatoire a été documentée selon le sexe, le groupe d’âge et le stade de la maladie. La section pyramidale a été administrée à trois reprises par deux physiothérapeutes, à deux semaines d’intervalle, pour évaluer la fidélité intra/interévaluateurs. Résultats : La validité de contenu a été jugée adéquate par les experts du domaine. La validité de construit convergente est soutenue par des corrélations élevées avec les outils mesurant des concepts apparentés (r > 0,7, p = 0,00), à l’exception du SF-12v2 (r = 0,09-0,33). La validité de construit discriminatoire est appuyée par la capacité de distinguer les personnes atteintes en fonction des groupes d’âge et des stades de la maladie. La fidélité intra/interévaluateurs est excellente pour les items individuels (κ[indice inférieur w] = 0,68-0,96/0,60-0,95 sauf pour deux items κ[indice inférieur w] = 0,12 et 0,47) et pour le sous-total pyramidal (CCI = 0,94/0,88, p = 0,000). La cohérence interne (α = 0,85) témoigne de l’homogénéité des items pyramidaux. Conclusion : Le sous-total pyramidal du DSI-ARSACS a démontré une excellente validité de construit convergente et discriminatoire et une bonne fidélité. L’échelle de gravité permettra de mieux documenter l’évolution naturelle de la maladie. / Abstract : Introduction: Autosomal recessive spastic ataxia of Charlevoix-Saguenay (ARSACS) is a hereditary and degenerative illness that has a high carrier rate (1/22) in Saguenay-Lac-St-Jean (Quebec, Canada) but that is also found elsewhere around the world. Individuals with ARSACS have cerebellar impairments (ataxia), neuropathic impairments (amyotrophy) and pyramidal impairments (spasticity). ARSACS does not have the same characteristics as other forms of ataxia and there is currently no specific disease severity index (DSI) for it. Method: This project aimed to develop the items of the pyramidal section of the DSI-ARSACS and document their metrological properties. A literature review was conducted to identify ARSACS’ related impairments and existing scales measuring pyramidal impairments. Both items from known scales and new items were used to build a new scale that would assess the pyramidal impairments associated with ARSACS. The scale’s content validation was based on expert opinion. A consensus on the final scale composition was reached. Two physiotherapists administered the newly developed scale to 28 participants with a genetically confirmed ARSACS diagnosis in order to document the reliability of the pyramidal section of the DSI. Existing scales related to pyramidal impairments, mobility, social participation and quality of life were administered to assess convergent construct validity. The contrasting group method (age group, disease stage, gender) was used to assess discriminant validity. Results: Content validity was considered adequate by an expert panel that completed a Delphi process. The pyramidal section’s subscore was distributed normally and did not show a ceiling/floor effect. Convergent construct validity was supported by strong correlations with existing scales measuring related constructs (r > 0.7, p = 0.00), excluding SF-12 v2 (r = 0.09-0.33). Discriminant construct validity was supported by the scale’s ability to distinguish subjects according to age and disease stage. Intra/inter-rater reliability was excellent for individual items (κ[subscript w] = 0.68-0.96/0.60-0.95), except for two items (κ[subscript w] = 0.12 and 0.47), and also excellent for the section’s subscore (CCI = 0.94/0.88, p = 0.000). Internal consistency (α = 0.85) reflected the homogeneity of the pyramidal items. Conclusion: The pyramidal section’s subscore of DSI-ARSACS displayed excellent metrological properties (discriminative and convergent validity, reliability) during this initial validation. The index will lead to a better understanding of ARSACS’ natural history while also allowing for the categorization of subjects participating in future clinical trials.

Author: Bc. Marie Hejnová Title: Effect of Functional Electrical Stimulation-Assisted Ergometry on Muscle Cross-Sectional Diameter, Nitrogen and Fluid Balance in Critically Ill Objectives: The aim of this thesis was to investigate the effect of functional electrical stimulation-assisted cycling ergometry (FES-CE) on cross-sectional diameter of the quadriceps femoris (QF) muscle of both lower extremities in critically ill patients. Another objective was to evaluate if the measured values are responding to the changes in muscle tissue or are caused by an oedema. Methods: The intervention group received daily intensified physical therapy and FES-CE. We measured cross-sectional diameter of the QF muscle repeatedly by a diagnostic ultrasound. We recorded daily nitrogen balance to objectivize catabolism of muscle and fluid balance to objectivize amount of cumulative fluid. Results: The total of 115 patients were evaluated. Average decrease of cross-sectional diameter of QF muscle in the intervention group was 0.020 ± 0.070 cm/day, in the control group it was 0.017 ± 0.084 cm/day (p = 0.87). We registered an opposite result from the eighth day onwards, the intervention group had average decrease 0.025 ± 0.047 cm/day and the control group 0.040 ± 0.076 cm/day (p = 0.38). The nitrogen intake was...

INTRODUÇÃO: A doença renal crônica (DRC) é uma patologia progressiva e debilitante, que apresenta alta mortalidade devido a causas cardiovasculares. Pacientes com DRC apresentam alterações metabólicas e musculares que estão associadas com diminuição da capacidade funcional e baixa tolerância ao exercício, porém pouco se sabe sobre o acometimento da musculatura respiratória desses pacientes. Dessa forma, os objetivos primários deste estudo foram avaliar a força muscular respiratória (FMR) de pacientes com DRC e verificar a existência de associação da força da musculatura inspiratória com fatores de risco cardiovasculares já descritos na DRC. MÉTODOS: A amostra foi composta por pacientes com DRC (estádios 3 ao 5) (grupo DRC, n = 30) e por indivíduos saudáveis (grupo controle, C. n =11). Posteriormente, para fins de comparação, os pacientes com DRC foram divididos em dois grupos: pacientes com DRC em fase não dialítica (estádios 3 e 4 - grupo DRC-ND, n=12) e pacientes com DRC em hemodiálise (estádio 5 - grupo DRC-D, n = 18). Todos os indivíduos realizaram os seguintes procedimentos: manovacuometria digital para mensuração da pressão inspiratória máxima (PImax) e pressão expiratória máxima (PEmax); registro da pressão arterial (PA) batimento a batimento e do eletrocardiograma para mensuração das variáveis hemodinâmicas; registro da atividade simpática nervosa muscular (ANSM); avaliação da composição corporal por meio de bioimpedância; avaliação da velocidade de onda de pulso (VOP) carotídea-femoral; avaliação da função endotelial; teste ergoespirométrico para mensuração da capacidade funcional cardiorrespiratória. Para os indivíduos do grupo DRC-D as avaliações foram sempre realizadas no segundo dia interdialítico da semana. Posteriormente as curvas de pressão arterial registradas foram utilizadas para mensurar a variabilidade da frequência cardíaca (VFC) e da PA e para determinar o barorreflexo espontâneo. RESULTADOS: Os pacientes com DRC apresentam redução da FMR quando comparados ao grupo controle (PImax: DRC= 82,51 ± 24,39 vs. C= 115,20 ± 18,71 cmH2O; PEmax: DRC= 99,64 ± 19,86 vs. C= 138,90 ± 27,08 cmH2O). Não houve diferença nas pressões respiratórias entre os grupos DRC-D e DRC-ND. Além disso, os pacientes com DRC apresentam diminuição da VFC [SDNN: DRC = 19,03 (10,95 - 44,28) vs. C= 45,25 (28,45 - 76,86)ms], aumento do balanço simpatovagal (DRC= 3,42 ± 1,99 vs. C= 1,54 ±1,01), aumento da variância da PA sistólica [DRC= 48,60 (13,38 -149,00) vs. C= 29,76 (15,83 - 49,54) mmHg2, prejuízo tanto da ativação (DRC= 0,40 ± 0,15 vs. C= 0,72 ± 0,10) quanto da sensibilidade barorreflexa (DRC= 7,98 ± 4,37 vs. C= 20,87 ± 10,68 ms/mmHg), bem como, aumento da ANSM (DRC= 20,44 ± 3,88 vs. C= 17,75 ± 1,46 bursts/min). Para a maioria dos índices de VFC o grupo DRC-D apresentou maior comprometimento do que o grupo DRC-ND. Contudo, o balanço simpatovagal, a variância da PA sistólica, a ANSM e a ativação do barorreflexo não foi diferente entre os grupos DRC-D e DRC-ND. Além disso, os pacientes com DRC apresentaram menor consumo de oxigênio que os indivíduos saudáveis (DRC= 29,1 ± 7,76 vs. C= 38,5 ± 7,9 ml/kg/min), redução da função endotelial (DRC= 4,90 ± 4,62 vs. C =8,70 ± 2,19%) e aumento da VOP (DRC= 8,30 (6,15 - 12,2) vs. C= 6,55 (5,4 - 7,8) m/s) quando comparado ao grupo controle, sendo que não foram observadas diferenças entre os grupos DRC-D e DRC-ND para estas variáveis. Quanto a composição corporal, os indivíduos com DRC apresentaram menor massa corporal celular, menor massa magra, maior massa gorda, menor água intracelular, e maior porcentagem de água extracelular quando comparados ao grupo controle. Não foram observadas diferenças na composição corporal entre o grupo DRC-D e DRC-ND. Houve associação positiva entre a força muscular inspiratória e o consumo máximo de oxigênio, bem como entre a PImax e níveis séricos de albumina nos indivíduos com DRC. CONCLUSÕES: Pacientes com DRC, mesmo em fase não dialítica, apresentam comprometimento da FMR, principalmente da PImax, bem como redução da capacidade funcional cardiorrespiratória, sendo que, existe uma associação entre a PImax e o consumo máximo de oxigênio. Além disso, os pacientes com DRC apresentam prejuízo da VFC e da sensibilidade barorreflexa, aumento do balanço simpatovagal, da ANSM e alterações vasculares, que embora pareçam ser mais evidentes nos doentes renais em fase dialítica, já podem ser observadas também na fase pré-dialítica da DRC / INTRODUCTION: Chronic kidney disease (CKD) is a progressive and debilitating condition that presents high mortality due to cardiovascular causes. Patients with CKD have metabolic and muscular changes that are associated with decreased functional capacity and low tolerance to exercise, but little is known about the involvement of the respiratory muscles in these population. Thus, the primary objectives of this study were to evaluate the respiratory muscle strength (RMS) of patients with CKD and to verify the existence of an association of inspiratory muscle strength with cardiovascular risk factors already described in CKD. METHODS: The sample consisted of patients with CKD (stages 3 to 5) (CKD group, n = 30) and healthy individuals (control group, C n = 11). For comparison purposes, patients with CKD were divided into two groups: non-dialytic CKD patients (stages 3 and 4 - CKD-ND group, n = 12) and patients with CKD on hemodialysis (stage 5 - group CKD-D, n = 18). All subjects performed the following procedures: digital manovacuometry to measure maximal inspiratory pressure (MIP) and maximal expiratory pressure (MEP); recording of blood pressure (BP) beat-to-beat and electrocardiogram for measurement of hemodynamic variables; register of sympathetic nervous muscle activity (SNMA); assessment of body composition by bioimpedance; assessment of carotid-femoral pulse wave velocity (PWV); evaluation of endothelial function; ergospirometric test for measurement of cardiorespiratory functional capacity. For the subjects in the CKD-D group the evaluations were always performed on the second interdialytic day of the week. Subsequently, the recorded blood pressure curves were used to measure heart rate (HRV) and BP variability and to determine spontaneous baroreflex. RESULTS: Patients with CKD had a reduction in RMS when compared to the control group (MIP: CKD = 82.51 ± 24.39 vs. C = 115.20 ± 18.71 cmH2O; MEP: CKD = 99.64 ± 19, 86 vs. C = 138.90 ± 27.08 cm H2O). There was no difference in respiratory pressures between the CKD-D and the CKD-ND groups. In addition, patients with CKD had a decrease in HRV [SDNN: CKD = 19.03 (10.95 - 44.28) vs. C = 45.25 (28.45 - 76.86) ms], increased sympatovagal balance (CKD = 3.42 ± 1.99 vs. C = 1.54 ± 1.01), increased systolic BP variance [CKD = 48.60 (13.38 -149.00) vs. C = 29.76 (15.83 - 49.54) mmHg2, impairment of both activation (CKD = 0.40 ± 0.15 vs C = 0.72 ± 0.10) and baroreflex sensitivity (CKD = 7.98 ± 4.37 vs. C = 20.87 ± 10.68 ms/mmHg), as well as increased SNMA (CKD = 20.44 ± 3.88 vs. C = 17.75 ± 1.46 bursts/min). For most HRV scores, the CKD-D group presented greater impairment than the CKD-ND group. However, sympathovagal balance, systolic BP variance, SNMA and baroreflex activation were not different between the CKD-D and CKD-ND groups. In addition, patients with CKD had lower oxygen consumption than healthy subjects (CKD = 29.1 ± 7.76 vs. C = 38.5 ± 7.9 ml/kg/min), reduction of endothelial function (CKD = 4.90 ± 4.62 vs. C = 8.70 ± 2.19 %) and increased PWV (CKD = 8.30 (6.15 - 12.2) vs. C = 6.55 (5, 4 - 7.8) m/s) when compared to control group, and no differences were observed between the CKD-D and CKD-ND groups for these variables. Regarding body composition, individuals with CKD had lower cellular body mass, lower lean mass, higher fat mass, lower intracellular water, and higher percentage of extracellular water when compared to control group. No differences were observed in body composition between the CKD-D and CKD-ND groups. There was a positive association between inspiratory muscle strength and maximum oxygen consumption, as well as between MIP and serum albumin levels in individuals with CKD. CONCLUSIONS: Patients with CKD, even in the non-dialytic phase, have FMR impairment, mainly MIP, as well as reduction of cardiorespiratory functional capacity, and there is an association between MIP and maximal oxygen consumption in this population. In addition, patients with CKD have impairment of HRV and baroreflex sensitivity, increased sympatovagal balance, SNMA, and vascular alterations, that although they may appear to be more evident in renal dialysis patients, may also be observed in the predialytic phase of DRC

La dystrophie myotonique de type 1 (DM1), est une maladie génétique héréditaire affectant environ 1/8000 personnes. Les patients souffrant de DM1 développent essentiellement des troubles musculaires tels qu’une faiblesse et une atrophie musculaire. La cause de la DM1 est expliquée par la mutation du gène "DMPK". Lors de ma thèse, j’ai pu démontrer que l’épissage de l’ARNm BIN1 était altéré dans le muscle DM1. En effet, l’exon 7 de BIN1, qui est absent du muscle normal, est exprimé de façon aberrante chez les patients DM1. En utilisant un modèle murin, j’ai prouvé que l’expression forcée de l’exon 7 de BIN1 altérait simultanément la structure et la fonction du muscle. Nous avons notamment observés une diminution de la taille des fibres musculaires et une augmentation de la faiblesse musculaire, comparé à des souris normales. Par conséquent, ce travail aidera à la compréhension du mécanisme de la maladie et pourrait expliquer les causes de la faiblesse musculaire et de l’atrophie. / Myotonic dystrophy of type 1 (DM1), is an inherited genetic disease affecting around 1 in 8000 person. Patients suffering from DM1 develop essentially muscle disorders such as muscle weakness, muscle loss and atrophy. The cause of DM1 is explained by the mutation of a gene called “DMPK“.During my thesis, I discovered that the alternative splicing of BIN1 mRNA was altered in the muscle of DM1 patients. Indeed, the BIN1 exon 7, which is normally absent in healthy muscle, is aberrantly expressed in DM1 muscle. By using a mouse model, I found that the forced expression of BIN1 exon 7 was responsible of the alteration of both muscle structure and function. Notably, we found a decrease in muscle fibers area (atrophy) and an increase of muscle weakness, compared to wild-type mice. Therefore, this work will help in the understanding of the disease mechanism and could explain the causes of muscle weakness and atrophy, which have never been elucidated to this date.

<p>Hronična opstruktivna bolest pluća (HOBP) jedna je od vodećih uzroka morbiditeta i mortaliteta &scaron;irom sveta. Uprkos stalnom napretku u medicini, uvođenju novih prognostičkih biomarkera, otkrivanju novih bronhodilatatornih, antiniflamatornih i antiinfektivnih lekova, ova bolest i danas beleži stalan porast broja obolelih i umrlih. Prema savremenom tumačenju HOBP je heterogena bolest koja je udružena sa brojnim komorbiditetima i sistemskim manifestacijama. Zajednički faktori rizika su osnova za javljanje udruženih hroničnih bolesti. Komorbiditeti i akutne egzacerbacije doprinose ukupnoj težini bolesti. S obzirom da se HOBP manifestuje i izvan pluća kod svakog pacijenta je neophodno proceniti postojanje sistemskih manifestacija i tragati za komorbiditetima. U reviziji &bdquo;Globalne strategije za dijagnozu, lečenje i prevenciju hronične opstruktivne bolesti pluća GOLD‖ iz 2011. godine navedene sledeće pridružene bolesti za kojima je potrebno aktivno tragati: kardiovaskularne bolesti, disfunkcija skeletnih mi&scaron;ića, metabolički sindrom, osteoporoza, depresija i karcinom pluća, bronhiektazije. Lečenje HOBP delimo u dve velike grupe: farmakolo&scaron;ko i nefarmakolo&scaron;ko. Farmakolo&scaron;ko lečenje prema GOLD-u, danas se zasniva na stepenastom pristupu. Treba ga sprovodi kod svakog pacijenta sa simptomima. Poslednjih godina na značaju veoma dobija nefarmakolo&scaron;ko lečenje pacijenata sa HOBP, zbog sve vi&scaron;e dokaza o pozitivnom efektu na smanjenje simptoma bolesti, popravljanja tolerancije na napor, smanjenje egzacerbacija. U nefarmakolo&scaron;ko lečenje ubrajamo: aktivno izbegavanje faktora rizika, prestanak pu&scaron;enja, oksigenoterapiju, vakcinaciju protiv gripa, psihosocijalnu podr&scaron;ku, respiratornu rehabilitaciju (RR) i hirur&scaron;ko lečenje. Danas se zna da RR ostvaruje brojne benefite kod pacijenata sa HOBP, kao i da je većina tih benefita zasnovana na dokazima (GOLD 2013): pobolj&scaron;ava kapacitet za vežbanje, smanjene osećaja nedostatka vazduha, pobolj&scaron;ava kvalitet života, smanjuje broj hospitalizacija i dužinu hospitalizacije, smanjuje anksioznost i depresiju povezane sa HOBP, efekti traju i nakon zavr&scaron;enog programa rehabilitacije, pobolj&scaron;ava preživljavanje ovih pacijenata. Primarni ciljevi na&scaron;eg istraţivanja bili su da se utvrdi procenat ispitanika kod kojih je ostvaren pozitivan ishod respiratorne rehabilitacije, da se odredi povezanost sledećih faktora sa ishodom respiratorne rehabilitacije: pol, godine života, &bdquo;pack/years―, dužina trajanja bolesti, broj egzacerbacija u prethodnoj godini, pridružena oboljenja: ishemijska bolest srca, srčana insuficijencija, hipertenzija, osteoporoza, depresija, dijabetes, bronhiektazije, karcinom pluća, tuberkuloza pluća. Takođe smo želeli da utvrdimo i uticaj sledećih parametara na ishod rr:FEV1, BMI, satO2, 6-minutni test hoda, &bdquo;CAT― upitnik, &bdquo;mMRC― upitnik, BODE indeks. Urađena je retrospektivno-prospektivna studija, koja je uključila 500 pacijenata sa HOBP, svih stadijuma I-IV , u stabilnoj fazi bolesti, koji su u toku dvogodi&scaron;njeg perioda odradili kompletan program ambulantne respiratorne rehabilitacije. Program je sprovođen u Poliklinici za plućne bolesti, Instituta za plućne bolesti Vojvodine. Dobijeni rezultati pokazali su da je 452 pacijenta (90,4%) ostvarilo pozitivan ishod RR: najvi&scaron;e ispitanika 142 (28,4%) bilo je u kategoriji vrlo dobar, potom slede kategorije dobar sa 129 ispitanika (25,8%), zadovoljavajući sa 102 ispitanika (20,4%), i na kraju kategorija odličan sa ukupno 79 (15,8%) ispitanika. Nakon programa RR do&scaron;lo je do statistički značajnih pobolj&scaron;anja u vrednostima FEV1, 6MTH, satO2, CAT, mMRC, BODE indeksa. Pol, starost, pu&scaron;ački status, dužina trajanja bolesti i &ge;2 egzacerbacije u prethodnoj godini nemaju uticaja na uspe&scaron;an ishod RR. Utvrđeno je postojanje statistički značajne negativne korelacije između srčane slabosti i pozitivnog ishoda respiratorne rehabilitacije, dok nije nađena statistički značajna povezanost ostalih ispitivanih komorbiditeta sa pozitivnim ishodom respiratorne rehabilitacije. Kao statistički značajni univarijantni prediktori pozitivnog ishoda respiratorne rehabilitacije jesu: manji broj pridruženih bolesti, odsustvo srčane slabosti, niža saturacija hemoglobin kiseonikom, veći BMI, mMRC &ge; 2, CAT &ge; 10, B i D stadijumi bolesti, dok je multivarijantnom logističkom regresionom analizom pokazano da su nezavisni prediktori pozitivnog ishoda respiratorne rehabilitacije: manji broj pridruženih bolesti, odsustvo srčane slabosti, veći BMI, CAT &ge; 10.</p> / <p>Chronic obstructive pulmonary disease (COPD) is one of the leading morbidity and mortality causes all over the world. Despite the steady advance in scientific research, introduction of novel prognostic biomarkers, new and potent bronchodilation, anti-inflammatory and anti-infectious drugs, a constant increase in the number of the affected and deceased from chronic obstructive pulmonary diseas has still been permanently evidenced in the 21st century. In a modern concept, the chronic obstructive pulmonary disease (COPD) is understood as a heterogenous disorder associated with numerous comorbidities and systemic manifestations. Common risk factors represent the basis for concomitant chronic diseases to develop. Comorbidities and acute exacerbations contribute to the overall disease severity. As a COPD may develop extrapulmonary manifestations as well, each patient should be evaluated for systemic manifestations and comorbidities. The 2011 update of the &bdquo;Global Strategy for Chronic Obstructive Lung Disease Diagnosis, Management, and Prevention &ndash;GOLD‖ lists the following comorbidities to be actively searched for: cardiovascular diseases, skeletal muscle dysfunction, metabolic syndrome, osteoporosis, depression, lung cancer and bronchiectases. The treatment of COPD can be devided in two groups: pharmacological and non-pharmacological. Pharmacological treatment is today, according to GOLD, based on incremental approach. It should be carry out in every patient with simptoms. In last few years, non-pharmacological treatment of COPD is very popular, due to the evidence of positive effects on decreasing the simptoms, increasing the tolerance to exertion and decreasing the exacerbations. Non-pharmacological treatment consider: active avoiding the risk factors, smoking cessation, oxigenotherapy, vaccination against the flu, psicho-social support, respiratory rehabilitation and surgery. It is well known today that respiratory rehabilitation achieve numerous benefits in COPD patients and most of that benefits are evidence based (GOLD 2013): increasing the exercise capacity, decreasing the shortness of breath, increasing the quality of life, reduces the number and length of hospital stay, decreasing the anxiety and depression conected to COPD, the effects lasts and after the rehabilitation program, improves the survival of this patients. The primary goals of this investigation were to establish the percentage of patients with positive outcome after the respiratory rehabilitation, to determine the conection of the following factors with the outcome of respiratory rehabilitation: gender, age, &bdquo;pack/years―, duration of the disease, the number of exacerbations in previous year, comorbidities: ischemic heart disease, heart failure, arterial hypertension, osteoporosis, depression, diabetes mellitus, bronchiectasis, lung cancer, tuberculosis. The other goals were to establish the influence of some parametars on the outcome of respiratory rehabilitation: FEV1, BMI, SaO2 ,6 minute walk test, &bdquo;CAT― questionnaire, &bdquo;mMRC― questionnaire, BODE index. This was retrospective-prospective study the included 500 patients with COPD, from I to IV stadium, in stable disease, who have done the two years complete program of ambulatory respiratory rehabilitation. The program have been done in polyclinic for respiratory diseases, Institute for pulmonary disesases of Vojvodina, Sremska Kamenica. The results showed that 452 patients (90,4%) achieved positive outcome of respiratory rehabilitation. The majority of patients 142 (28,4%) were in ―very good‖ caterogy, the 129 patients (25,8%) in category ―good‖, ―satisfied‖ 102 patients (20,4%) and ―excellent‖ 79 patients (15.8%). After completion of the respiratory rehabilitation program, statistically significant improvements of the following parameters have been achieved: FEV1, 6MTH, SaO2, mMRC, BODE index. Gender, age, smoking, duration of the disease and &ge;2 exacerbations in previous year did not have influence on the successful respiratory rehabilitation outcome. The statistically significant negative correlation between the heart failure and positive respiratory rehabilitation outcome has been achieved, while there were no statistically significant correlations among other comorbidities and the successful respiratory rehabilitation outcome. The statistically significant univariant predictors of positive outcome of respiratory rehabilitation are: less comorbidities, absence of heart failure, lower oxygen saturation, higher BMI, , mMRC &ge; 2, CAT &ge; 10, B i D stadium of disease, while multivariant logistic regression analysis showed that the independent predictors of positive outcome of respiratory rehabilitation are: less comorbidities, absence of heart failure, higher BMI, CAT &ge; 10.</p>